Nicotinic acid production



Filed NOV. 1, 1947 INVENTOR {Val/er flan/(ml ATTORNEY Patented Feb. 26,1952 V NICOTINIC ACID PRODUCTION Walter G. Frankenburg, Millersville,Pa., assignor to General Cigar Co., Inc., New York, N. Y., a

corporation of New York Application November 1, 1947, Serial No. 783,553

15 Claims. 1

This invention relates to the production of nicotinic acid and, moreparticularly, to the conversion of nicotine in tobacco to nicotinicacid.

Nicotinic acid or niacin has received very considerable attentionbecause of its prominence in the vitamin field. The production of thischemical compound has been the subject of intensive research which hasled to the development of several chemical processes centering chieflyaround the oxidation of nicotine, quinoline or beta-picoline by strongchemical oxidants like sulfuric and nitric acids. The current largescaleproduction of nicotinic acid in this country relies principally onquinoline and betapicoline derived from coal tar because of priceadvantage over nicotine'which is laboriously extracted from tobacco.

A principal object of this invention is to provide an economical processfor converting the nictoine in tobacco to nicotinic acid.

Another important object is to convert the nicotine in tobacco tonicotinic acid without recourse to expensive chemical oxidants.

A further object is to open a commercial outlet for tobacco waste, dustand trimmings and tobacco not suitable for smoking purposes, whichclasses of tobacco are commonly considered to be a total loss, byconverting the nicotine content of such tobacco directly to valuablenicotinic acidv Additional objects and advantages of my invention willbe evident from the description which follows.

I have discovered that nicotine in tobacco can be converted to nicotinicacid in situ, thus elimi-- nating the costly preliminary step ofextracting nicotine from tobacco. The significance of this discovery ismore fully appreciated when it is remembered that prior processes forproducing nicotinic acid from nicotine have in essence involved twotedious extractions: one for separating nicotine from tobacco and theother for separating nicotinic acid from the complex reaction massresulting from the oxidation of nicotine by chemical oxidants. Theinvention makes it possible to derive nicotinic acid from tobacco with asingle extraction.

An important aspect of my discovery is the conversion or oxidation ofnicotine in tobacco to nicotinic acid essentially by means of ordinaryair or gas containing free oxygen. The expense of powerful chemicaloxidants, conventionally used in the oxidation of extracted nicotine, isthus circumvented. I have also found that chemical agents can be addedto the tobacco to facilitate or hasten the oxidation of its nicotine byfree oxygen but these chemical agents are employed in limited quantitiessince they appear to function as catalysts. Furthermore, suchcatalyst-like agents are often recoverable from the treated tobacco andmay be reused in the treatment of additional tobacco by the process ofmy invention to produce more nicotinic acid. It is thus seen that littleor no expenditure is made for chemicals in oxidizing nicotine in tobaccoto nicotinic acid as taught herein.

More specifically, I take harvested tobacco, the term, tobacco, beingherein intended to embrace any plant material containing nicotine, andexpose it to an oxygen-containing atmosphere under conditions favoringfermentation. It is in the course of fermentation that the nicotine inthe tobacco is converted to nicotinic acid. It is advantageous tocomminute the tobacco so as to expose a larger surface area to thereaction; accordingly, shredding or, better still, grinding of thetobacco as with a hammer-type pulverizer to form a powder, say passingthrou h a 40-mesh screen, is carried out in most cases. The tobacco usedin my process has usually been cured, i. e., it has been hung to dryuntil it has turned brown. When tobacco scraps or trimmings resultingfrom the manufacture of cigars and other smoking products are utilizedin my process, such tobacco will have been also sweated and fermented(resweated) in accordance with common practices in the tobacco industry.Fermented tobacco is frequently referred to as resweated tobacco becausethe preliminary sweating is a mild, slow form of fermentation.

As previously stated, the conversion of the nicotine in tobacco tonicotinic acid pursuant to my invention involves exposing tobacco,preferably in comminuted form, to an oxygen-containing atmosphere underconditions inducing fermentation. 'As known to tobacco experts, ieramentation is promoted by moisture which may be added directly as waterto the tobacco, for instance, by spraying water on the tobacco, orindirectly by humidifying the oxygen-containing atmosphere in which thedesired reaction in the tobacco is to be effected. While conventionalfermentation is aimed at making tobacco acceptable by smoking standardssuch as mellowness and aroma and is therefore carefully controlled todevelop the desired qualities in the tobacco because prolonged or strongfermentation will destroy the same qualities which are sought, I favorstrong and continued fermentation to the end that the nicotine contentof the tobacco may be substantially completely converted to nicotinic 3acid. In short, for the purposes of my invention, the tobacco isfermented to an extent where it is no longer suited for smokingproducts.

Deep fermentation can be achieved by methods well known in the tobaccoindustry but it is ad- -visable to take steps which shorten the reactiontime. One of the accelerating steps has previously been mentioned,namely, comminution of the tobacco. Another is to conduct the fermentingreaction at elevated temperatures above those prevailing when tobacco isfermented preparatory to its use in cigars, cigarettes and the like. Areaction temperature above about 130 F. is desirable, preferably in therange of about 150 to 220 F. Excessive temperatures leading tospontaneous combustion of the reaction mass are obviously to be avoided.

Moisture is an important factor in tobacco fermentation and is mostreadily controlled by the humidity of the oxygen-containing atmospherein which fermentation proceeds. It is usually advisable to maintain arelative humidity of at least about 60 humidities of at least about 80%are frequently advantageous.

In addition, I have found that there are chemical substances which whenadded in minor proportions to the reactin or fermenting tobacco functionlike catalysts to accelerate and/or drive closer to completion theoxidation of the nicotine in the tobacco to nicotinic acid.Water-soluble compounds of elements of Series 4 of the Mendeleeifperiodic table having atomic numbers to 28 (Mn, Fe, Co and Ni),inclusive, are efiective catalysts. These catalysts are usually appliedto the tobacco before fermentation in the form of an aqueous solutioneither by spraying the solution or by dipping the tobacco in thesolution, It is advisable to select compounds, generally metal salts,which are stable under the reaction conditions. Manganese and ironcatalysts are preferred. Catalysts comprising two metals either asphysical mixtures of two metal compounds or as single complex compoundscontaining the desired metals are often used to advantage. Such salts ofthe catalytic metals as the nitrates, sulfates, acetates,citrates andtartrates represent suitable catalysts for the process of my invention.The proportion of catalysts added is generally not more than 1% byweight of the dry tobacco, and frequently not more than 0.5%, theforegoing percentages being based on the molecular weight of thecatalytic element or metal in the catalyst compound. In my copendinapplication Serial No. 783,626, filed November 1, 1947, the use of theforegoing catalysts in the fermenting or resweating of tobacco to yieldsmoking grade tobacco is fully disclosed; said copending applicationcontains generic claims to the use of fermentation catalysts.

Another factor which permits promotion and regulation of the conversionof nicotine in tobacco to nicotinic acid is pH. The maintenance of a pHin the acid range, especially a pH of about 3 to 6.5, is beneficial. Forthis purpose, a sufier system such as a mixture of disodium phosphateand citric acid may advantageously be introduced by addition to waterwhich is sprayed on the tobacco. In many cases, however, the addition ofa buffer solution is unnecessary because the tobacco contains a naturalbuifer system which keeps its pH in the acid range.

Further refinements of the process which I have developed includepressure changes and wetting agents. By subjecting tobacco to a reducedpressure, say below 50 mm. Hg absolute, and immersing the thusvacuumized tobacco in water or an aqueous catalyst solution, the liquidinfiltrates more thoroughly and quickly into the tobacco because theplant cells are at least partially evacuated of gas which tends toobstruct the pentration of liquid. Wetting agents added to the water oraqueous catalyst solution also function to drive the liquid into thetobacco and thus aid in the fermentation process. Less than 0.05% byweight of wetting agents like sulfonated alcohols or sulfonatedalkyl-benzenes dissolved in water materially improves the penetration ofthe liquid into the tobacco.

While my process of fermenting tobacco to produce nicotinic acid may becarried out by disposing the tobacco in bins, cases, trays or reticularcontainers and exposing the thus arranged tobacco to air, moisture andother desired conditions of fermentation, I prefer to agitate the tobacco so that fermentation or oxidation of nicotine proceeds uniformlyand rapidly therethrough. Tumbling drums or other rotary reactionvessels are convenient devices in which my process may be performed.

For further elucidation of my invention, reference is now made to thedrawing accompanying this specification and formin a part thereof. Thedrawing is a schematic elevation, partly in section, of a fluidizingvessel or reactor in which a preferred embodiment of my invention may becarried out.

An elongate cylindrical vessel I0 is provided at its lower end with aconical section II to which is connected pipe 12 having rotarybucket-type valve 13 for withdrawing comminuted tobacco from vessel l0.An inlet pipe l4 terminating in a discharge nozzle IS in the bottom ofconical section II serves to introduce the gaseou stream required forthe treatment of the tobacco in accordance with my invention. Vessel I0holds a charge or bed of comminuted tobacco, say tobacco ground to passthrough a 40-mesh screen, maintained in a fluidized state by the gasousstream discharging from nozzle 15. The fluidized tobacco bed l6 has apseudo-liquid level I'. which is the region where the gases risingthrough bed [6 disengage themselves from the bulb of the tobaccoparticles. The gases ascend through settling space l8 which is of largerdiameter than the portion of vessel l0 holding the fluidized bed l6;because of the enlarged cross-section of space IS, the gases movetherethrough at a decreased velocity and this minimizes the entrainmentof tobacco particles by the gases leaving vessel I0 through outlet pipe19. The gaseous efiiuent is conducted by pipe 20 to cloth bag filters 2|and 22 which recover the fine tobacco particles usually inevitablycarried out of vessel III by the gaseous eilluent. Valves 23 and 24serve to cut off the gaseous stream from filters 2| and 22,respectively, so that one filter may be emptied of recovered tobaccopowder while the other filter is on stream for the separation ofadditional quantities of tobacco powder from the gases passingtherethrough. Other devices such as cyclone separators and electricalprecipitators may be substituted for the bag filters 2l and 22.

The comminuted tobacco is conveniently supplied to vessel ID from hopper25 by means of screw conveyor 26. When desired, the fluidized mass l6may be heated to any required temperature by passing steam or otherheating medium through jacket 2'! surrounding the lower portion ofvessel l0.

The equipment shown in the drawing may be operated batchwise orcontinuously. Batchwise opera tion involves charging into vessel l I aquantity of tobacco powder which when fluidized by a stream of air fromnozzle I forms the fluidized bed It. Moisture to assist the reaction maybe introduced by mixing steam with the air passing through vessel 10.The-mixed gases are supplied at a rate such that the mass of tobaccopowder in vessel l0 assumes a turbulence resembling that of a boilingliquid and is, therefore, said to be fluidized. The fluidizing techniqueis best known for its application to the catalytic cracking of petroleumhydrocarbons and is widely described in the technical literature, e. g.,Chemical and Metallurgical Engineering, June 1944. pages 94 et seq.

As known, the gas velocity necessary to give good fiuidizing resultswill vary in each case with such factors as particle size, shape anddensity, and gas density and viscosity. However, with tobacco incomminuted form, a gas velocity of not more than about 1 foot per secondis generally satisfactory; a velocity in the range of about 0.1 to 0.5foot per second is usually preferred.

Fluidization of the tobacco powder at a suitable reaction temperature,say 200' F., is continued until a sample of tobacco withdrawnperiodically from vessel Ill shows that the conversion of the nicotinein the tobacco to nicotinic acid has proceeded to the desired extent.The temperature in vessel I0 may be maintained by preheating the gasespassing therethrough and/or by flowing steam through jacket 21. Havingreached the desired extent of conversion, the tobacco powder iswithdrawn from vessel II by opening valve I! in outlet pipe I2. Thedischarged powder may be made to fall directly into a tank containingthe liquid used to extract the nicotinic acid from the tobacco.

To operate on a continuous basis, comminuted tobacco is fed to thefluidized bed I6 at regular intervals or continuously by means ofconveyor 26 and a corresponding amount of treated tobacco is withdrawnalso at regular intervals or continuously by way of valve l3. In suchcase, the vessel Ill must be made large enough to give the tobaccoparticles an average residence time in vessel I 0 adequate for asubstantial conversion of their nicotine content to nicotinic acid.'Where conditions for vigorous fermentation or reaction are maintained,a residence time of approximately 20 hours is generally satisfactory. Itis well to note at this point that if the conversion of nicotine tonicotinic acid has gone to completion, no significant harm is done incontinuing the exposure of the tobacco to the oxygen-containing gas andother conditions of reaction since nicotinic acid is a relatively stablecompound. Over-exposure of the tobacco powder is, of course, to beavoided because it decreases the productive throughput or capacity ofthe equipment.

With either batchwise or continuous operation, the moist air passingthrough the fluidized bed i6 flows through-line 20 to bag filters 2i and22 which catch any tobacco powder carried in suspension by the gaseousstream. The recovered tobacco, if its nicotine has not been sufficientlyoxidized to nicotinic acid, may be returned to vessel Ill for furthertreatment. Otherwise, it may be added to reacted tobacco which is readyfor the separation of nicotinic acid therefrom.

The recovery of nicotinic acid from the reacted tobacco can be effectedby diverse methods. One method involves a conventional extraction, forinstance, with gasoline'in the presence of lime to remove residualalkaloids from the tobacco, neutralization of the lime in the tobaccoand another extraction with a solvent for nicotinic acid. In anothermethod. the reacted tobacco is acidified by wettin'g it with a solutionof phosphoric or suli'uric acid and the acidified tobacco is extractedwith a nicotinic acid solvent such as methyl or ethyl alcohol, ethylether or chloroform. It will be understood that the extract containingthe nicotinic acid will usually contain other substances, e. g., citricand malic acids. Mixtures of nicotinic, citric and malic acids findvaluable uses in pharmacy and nutrition. Another alternative method isto extract the reacted tobacco with water, to precipitate any alkaloidsin the liquid extract through the addition of phosphotungstic orsilicotungstic acid, and to decant the liquid containing insolutionnicotinic acid and other substances, several of which havenutritional value.

Several procedures for separating nicotinic acid from complex mixtureshave been developed and are well known in the art. A common procedure isto bring the mixture to dryness, to dissolve from the resulting solidsthe nicotinic acid with hot water or alcohol. to filter off the solids,to cool the filtrate so as to crystallize the nicotinic acid, and toseparate the crystals by filtration. The crystals may be washed withcold water but, where further purification of the nicotinic acid isindicated, the crystals may be redissolved in hot water or alcohol, adecolorizing carbon suspended in the hot solution, the suspensionfiltered, and the filtrate cooled to recover crystallized nicotinicacid. Other procedures for isolating nicotinic acid involve itsprecipitation from solution as an insoluble metal salt, for instance, ascopper or zinc nicotinate. The insoluble salt is separated from theoriginal solution, is suspended in a strong aqueous solution of sodiumhydroxide so the nicotinate is converted to the soluble sodium saltwhile the metal is precipitated as the oxide, the insoluble metal oxideis removed by filtration, the alkaline filtrate is acidified to a pH ofabout 2, e. g., sulfuric acid, and allowed to stand until the nicotinicacid has crys tallized. The crystals are separated from the acidsolution and washed with cold water. If desired, further purificationmay be effected by redissolving and recrystallizing the nicotinic acid.Still another way to isolate the nicotinic acid in mixtures with othertobacco constituents is to bring such mixtures to dryness, to powder thesolid residues, and to subject these residues to vacuum sublimation; thenicotinic acid will sublime and condense in solid form on cooledsurfaces, in a condition of high purity.

A specific example of the process of my invention will be given in termsof the equipment shown in the drawing. Leaves of cured (dried) tobaccocontaining 3.8% by weight of nicotine are dipped in an aqueous solutioncontaining manganese sodium citrate (manganese citrate soluble N. F.VII) and iron ammonium citrate in the relative proportions of 1.0molecular weight of manganese to 1.5 molecular weight of iron.- Theleaves are dried and show that 0.2% by weight of manganese and 0.3% byweight of iron were added to the tobacco 'by the dipping opera-v throughvessel It! at a veiocity of about 0.25 foot per second and maintains thetobacco powder therein in a well fluidized state. The fluidized reactionmass I is maintained at a temperature of 205 F. Tobacco powder collectedin filters 2| and 22 from the gaseous eflluent of vessel I0 is returnedto hopper 25 for reintroduction into vessel l0. Tobacco powder in amountcommensurate to that fed to vessel In by conveyor 26 is regularlywithdrawn through outlet pipe l2 and valve I3. The tobacco powder has anaverage residence time of 22 hours in vessel l0 and in this period itsnicotine content is practically completely oxidized to nicotinic acid.

The reacted tobacco is then extracted with water or other suitablesolvent for nicotinic acid, like alcohol, and the nicotinic acidisolated from the liquid extract, for instance, by one of the proceduresoutlined hereinbefore.

Since the nicotine in the tobacco is converted to nicotinic acid by myprocess, the reacted tobacco, particularly after any residual alkaloidshave been eliminated, say by extraction or by steaming, is per se avaluable product which may be incorporated in cattle feed to enrich itsvitamin content. Another direct use of reacted tobacco containingnicotinic acid is as a high grade plant food. Accordingly, in somecases, the nicotine in tobacco may be oxidized to nicotinic acid andutilized without performing any costl extractions. Where the fermentedor reacted tobacco is to be used directly in a cattle feed or plantnutrient, the addition of catalysts for the iermentation must be madejudiciously or avoided completely as circumstances may dictate.

The surprisingly facile oxidation of nicotine in tobacco to nicotinicacid by free oxygen in accordance with my invention appears attributableto natural agents, perhaps catalysts, present in the tobacco. Thistheory seems to be corroborated by the fact that refined nicotine is notconverted to nicotinic acid by air and moisture under the conditions setforth in this specification but rather requires the use of strongchemical oxidants like nitric acid to effect the conversion. Regardlessof the exact nature of the reaction occurring in my process, it issufficient that nicotinic acid is produced by following the teachings ofthis specification. The term, fermentation, has herein been used in thesame general sense commonly understood in the tobacco industry; that isto say, the term does not imply that any process similar to the processof alcoholic fermentation occurs in tobacco and does not mean thatmicroorganisms are necessarily involved.

Those skilled in the art know that tobacco usually contains severalnicotine-type alkaloids, i. e., alkaloids like nicotine composed of thepyridine ring with another heterocyclic ring attached to its betaor3-position carbon, which are also oxidizable to nicotinic acid. Suchoxidizable nicotine-type alkaloids, notably nornicotine' and myosmine,can be converted to nicotinic acid by the process of my invention.

The foregoing description and examples are intended to be illustrativeonly. The many possible variations and modifications of my inventionconforming to its spirit are to be considered within the scope of theappended claims.

What I claim is:

1. In the conversion of tobacco nicotine to nicotinic acid, theimprovement which comprises reacting said nicotine while still in thetobacco with an oxygen-containing gas and moisture at a temperatureeffecting simultaneously fermenta- I tion of said tobacco, continuingthe reaction and simultaneous fermentation until said nicotine has beensubstantially completely consumed and the smoking qualities of saidtobacco have been destroyed, and thereafter recovering the resultantnicotinic acid from the thus fermented tobacco.

2. The process of claim 1 wherein the tobacco is in comminuted form.

3. The process of claim 1 wherein the tobacco has been cured andcomminuted.

4. The process for the production of nicotinic acid which comprisesadding to tobacco containing nicotine a water-soluble fermentationcatalyst containing an element selected from Series 4 of the Mendeleeffperiodic table and having an atomic number between 25 and 28, inclusive,fermenting said tobacco containing said catalyst with anoxygen-containing gas and moisture and continuing the fermentation untilsaid nicotine has been substantially completely consumed and the smokingqualities of said tobacco have been destroyed, whereby nicotinic acid isproduced, and thereafter separating the resulting nicotinic acid fromthe thus fermented tobacco.

5. The process of claim 4 wherein the tobacco has been cured andcomminuted.

6. The process of claim 4 wherein the catalyst comprises a water-solublemanganese compound.

7. The process of claim 4 wherein the catalyst comprises a water-solubleiron compound.

8. The fluidized process for the production of nicotinic acid whichcomprises fluidizing a mass of comminuted tobacco containing nicotinewith an oxygen-containing gas in the presence of moisture, the fluidizedmass having a turbulence resembling that of a boiling liquid, effectingfermentation of said tobacco and simultaneous conversion of saidnicotine to nicotinic acid within said fluidized mass until saidnicotine has substantially completely disappeared, and thereafterseparating product nicotinic acid from the thus treated tobacco.

9. The process of claim 8 wherein said fermentation and simultaneousconversion are effected at a temperature in the range of about to 220 F.

10. The process of claim 8 wherein the product nicotinic acid isseparated from the thus treated tobacco by extraction with water.

11. The process of claim 8 wherein the product nicotinic acid isseparated from the thus treated tobacco by extraction with alcohol.

12. The process for the production of nicotinic acid, which comprisesadding to tobacco containing nicotine a water-soluble fermentationcatalyst containing an element selected from Series 4 of the Mendeleeifperiodic table and having an atomic number between 25 and 28, inclusive,fermenting said tobacco containing said catalyst with anoxygen-containing gas and moisture and continuing the fermentation untilsaid nicotine has been substantially completely consumed and the smokingqualities of said tobacco have been r destroyed, whereby nicotinic acidis produced.

13. The process of claim 12 wherein the catalyst comprises awater-soluble iron compound.

14. The fluidized process for the production of nicotinic acid whichcomprises fluidizing a mass of comminuted tobacco containing nicotinewith an oxygen-containing gas in the presence of moisture, the fluidizedmass having a turbulence resembling that of a boiling liquid, andeffecting fermentation of said tobacco and simultaneous conversion ofsaid nicotine to nicotinic acid with- 10 in said fluidized mass untilsaid nicotine has sub- Number Name Date stantially completelydisappeared. 1,983,908 Lippmann Dec. 11, 1934 15. The process of claim14 wherein said fer- 2,172,531 Ekhard Sept. 12, 1939 mentation andsimultaneous conversion are effected. at a temperature in the range ofabout 5 FOREIGN PATENTS Number Country Date WALTER G. FRANKENBURG. 7 793Sweden of 1927 272,447 Great Britain of 1927 REFERENCES CITED 278,818Great Britain of 1927 The following references are of record in the 10471,854 Great Britain of 1937 file of this patent: r OTHER REFERENCESUNITED STATES PATENTS Vitamins, Rosenberg, 1942,p. 224.

Number Name Date Annual Review of Biochemistry, 1936, vol. V.

1,812,459 Vierling June so, 1931 p. 28.

1. IN THE CONVERSION OF TOBACCO NICOTINE TO NICOTINIC ACID, THEIMPROVEMENT WHICH COMPRISES REACTING SAID NICOTINE WHILE STILL IN THETOBACCO WITH AN OXYGEN-CONTAINING GAS AND MOISTURE AT A TEMPERATUREEFFECTING SIMULTANEOUSLY FERMENTATION OF SAID TOBACCO, CONTINUING THEREACTION AND SIMULTANEOUS FERMENTATION UNTIL SAID NICOTINE